Autophagy sensitivity of neuroendocrine lung tumor cells

Hong,Seung-Keun; Kim,Jin-Hwan; Starenki,Dmytro; Park,Jong-In

doi:10.3892/ijo.2013.2136

Autophagy sensitivity of neuroendocrine lung tumor cells

Authors:
- Seung-Keun Hong
- Jin-Hwan Kim
- Dmytro Starenki
- Jong-In Park
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Affiliations: Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI 53226, USA
Published online on: October 11, 2013 https://doi.org/10.3892/ijo.2013.2136
Pages: 2031-2038

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Abstract

Neuroendocrine (NE) phenotypes characterize a spectrum of lung tumors, including low-grade typical and intermediate-grade atypical carcinoid, high-grade large-cell NE carcinoma and small cell lung carcinoma. Currently, no effective treatments are available to cure NE lung tumors, demanding identification of biological features specific to these tumors. Here, we report that autophagy has an important role for NE lung tumor cell proliferation and survival. We found that the expression levels of the autophagy marker LC3 are relatively high in a panel of lung tumor cell lines expressing high levels of neuron-specific enolase (NSE), a key NE marker in lung tumors. In response to bafilomycin A1 and chloroquine, NE lung tumor cells exhibited cytotoxicity whereas non-NE lung tumor cells exhibited cytostasis, indicating a distinct role of autophagy for NE lung tumor cell survival. Intriguingly, in certain NE lung tumor cell lines, the levels of processed LC3 (LC3-II) were inversely correlated with AKT activity. When AKT activity was inhibited using AKTi or MK2206, the levels of LC3-II and SQSTM1/p62 were increased. In contrast, torin 1, rapamycin or mTOR knockdown increased p62 levels, suggesting that these two pathways have opposing effects on autophagy in certain NE lung tumors. Moreover, inhibition of one pathway resulted in reduced activity of the other, suggesting that these two pathways crosstalk in the tumors. These results suggest that NE lung tumor cells share a common feature of autophagy and are more sensitive to autophagy inhibition than non-NE lung tumor cells.

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